1. Field of the Invention
The present invention relates to an improved process for the purification of (.+-.)-2-azabicyclo[2.2.1]hept-5-en-3-one from its reaction solution.
2. Prior Art
(.+-.)-2-azabicyclo[2.2.1]hept-5-en-3-one is a starting material for the preparation of carbocyclic nucleoside analogues, which are of interest as therapeutic substances in medicine on account of their antiviral and chemotherapeutic properties.
The preparation of (.+-.)-2-azabicyclo[2.2.1]hept-5-en-3-one is mentioned for example in EP 0 508 352, but the process described in said patent utilizes exclusively organic solvents to prepare the desired compound. The advantage of this process is the high purity with which the (.+-.)-2-azabicyclo[2.2.1]hept-5-en-3-one can be recovered. The disadvantage, however, is the use of organic solvents in this reaction. Thus, advantageous modern processes all work with water as the reaction solvent.
The advantage of this modern variant is to be regarded as the fact that the entire synthesis can be carried out as a one-pot process starting from a suitable sulfinate, cyclopentadiene and cyanogen chloride. As one product of the reaction is the sulfinate used, this can successfully be recycled, making it possible substantially to reduce the operating costs of the process (EP 0 533 048 and DE 196 25 323).
In both the cases which have just been mentioned, the reaction solution advantageously prepared in this way is purified by extraction of the products into an organic solvent at pH values of approx. 8 in the aqueous phase.
The organic product phase is then concentrated and dried as described in EP 0 533 048 in order to isolate the product. The material obtained is orange or yellowish-brown in colour and has a content of &lt;96% (HPLC).
According to DE 196 25 323, (.+-.)-2-azabicyclo[2.2.1]hept-5-en-3-one can be crystallized from the organic phase after concentration. The losses of yield due to crystallization vary according to the position of the solubility equilibrium. Yields of light brownish-coloured product of &lt;75% with contents of 98-99% (HPLC) are thus obtained by this purification strategy.